Each year, approximately 6 million fractures occur in the United States. These fractures result in over 9 million physician visits and a loss of more than 36 million work days [1]. Fractures resulting in segmental defects of the long bones are particularly difficult to manage, often requiring multiple surgeries in an attempt to achieve adequate union and function [2].
There are many causes of segmental defects. They may be the result of many causes, including tumor resection, treatment of infection, failure of arthoplasty—but the most common cause is from trauma, particularly motor vehicle associated trauma. High energy, open fractures may result in direct immediate bone loss or may require debridement of devascularized contaminated bone. This is a common, yet challenging, problem for orthopaedic traumatologists and their patients. The incidence of severe lower extremity trauma in civilian life is certainly increasing due to the epidemic of road traffic accidents around the world. In the US alone, over a quarter million admissions annually are due to lower extremity injuries, and it is estimated that more than half are the result of high energy mechanisms [3].
The recent military conflicts around the world have also increased the need to address high energy or blast injuries which often involve bone trauma and tissue loss. Over 75% of modern war injuries involve the extremities, predominantly caused by fragments from explosive devices, which commonly cause open fractures with contaminated wounds and tissue loss [4]. These examples illustrate that there are needs in many areas of orthopaedics to improve bone healing.
Achieving bone union can be difficult in all aspects of orthopaedics, including spine, trauma, and upper extremity surgery. Failure to achieve bone union results in multiple additional surgeries, significant morbidity, and ultimately can lead to loss of extremity function or amputation for the patient. In cases of fracture nonunion alone, some 450,000 grafting procedures are performed yearly [5]. Many additional bone grafting procedures are required for spinal fusion. The gold standard for grafting to achieve bone union/fusion is the use of donor bone (called autograft) from the patient's hip. This often leaves a patient with a very painful donor site, which may not resolve. There is a need then for biologic enhancements for bone healing that do not require the harvesting of a patient's iliac crest hip bone trauma or tumour. Some aspects of the invention address this need.